Lorna P. Browne

Apparent Aortic Stiffness in Children with Pulmonary Arterial Hypertension

Background— Left ventricular dysfunction, mediated by ventricular interdependence, has been associated with negative outcomes in children with pulmonary arterial hypertension (PAH). Considering the dilation of the pulmonary arteries as a paramount sign of PAH, we hypothesized that the ascending aorta will present signs of apparent stiffness in children with PAH and that this effect may be because of mechanical interaction with the dilated main pulmonary artery (MPA). Methods and Results— Forty-two children with PAH and 26 age- and size-matched controls underwent comprehensive cardiac magnetic resonance evaluation. Assessment of aortic stiffness was evaluated by measuring pulse wave velocity, aortic strain, and distensibility. Children with PAH had significantly increased pulse wave velocity in the ascending aorta (3.4 versus 2.3 m/s for PAH and controls, respectively; P=0.001) and reduced aortic strain (23% versus 29%; P<0.0001) and distensibility (0.47 versus 0.64%/mm Hg; P=0.02). Indexed MPA diameter correlated with pulse wave velocity (P=0.04) and with aortic strain (P=0.02). The ratio of MPA to aortic size correlated with pulse wave velocity (P=0.0098), strain (P=0.0099), and distensibility (P=0.015). Furthermore, aortic relative area change was associated with left ventricular ejection fraction (P=0.045) and ventricular–vascular coupling ratio (P=0.042). Conclusions— Pediatric PAH patients have increased apparent ascending aortic stiffness, which was strongly associated with the degree of MPA distension. We speculate that distension of the MPA may play a major role in limiting full aortic expansion during systole, which modulates left ventricular performance and impacts systemic hemodynamics in pediatric PAH.

Effect of electrical dyssynchrony on left and right ventricular mechanics in children with pulmonary arterial hypertension

BACKGROUND Electrical and right ventricular (RV) mechanical dyssynchrony has been previously described in pediatric pulmonary arterial hypertension (PAH), but less is known about the relationship between electrical dyssynchrony and biventricular function. In this study we applied cardiac magnetic resonance (CMR) imaging to evaluate biventricular size and function with a focus on left ventricular (LV) strain mechanics in pediatric PAH patients with and without electrical dyssynchrony. METHODS Fifty-six children with PAH and comprehensive CMR evaluation were stratified based on QRS duration z-score, with electrical dyssynchrony defined as z-score ≥2. Comprehensive biventricular volumetric, dyssynchrony, and strain analysis was performed. RESULTS Nineteen PAH patients had or developed electrical dyssynchrony. Patients with electrical dyssynchrony had significantly reduced RV ejection fraction (35% vs 50%, p = 0.003) and greater end-diastolic (168 vs 112 ml/m2, p = 0.041) and end-systolic (119 vs 57, ml/m2, p = 0.026) volumes. Patients with electrical dyssynchrony had reduced RV longitudinal strain (-14% vs -19%, p = 0.007), LV circumferential strain measured at the free wall (-19% vs -22%, p = 0.047), and the LV longitudinal strain in the septal region (-10% vs -15%, p = 0.0268). LV mechanical intraventricular dyssynchrony was reduced in patients with electrical dyssynchrony at the LV free wall (43 vs 19 ms, p = 0.019). CONCLUSIONS The electrical dyssynchrony is associated with the reduced LV strain, enlarged RV volumes, and reduced biventricular function in children with PAH. CMR assessment of biventricular mechanical function with respect to QRS duration may help to detect pathophysiologic processes associated with progressed PAH.

Successful Treatment of Myocardial Infarction in an Infant With Kawasaki Disease

Although early treatment with intravenous immunoglobulin reduces the risk of coronary artery aneurysms, in refractory cases of Kawasaki disease, myocardial infarction can result from thrombosis of coronary artery aneurysms. Early recognition of myocardial infarction from Kawasaki disease myocarditis can reduce morbidity and mortality. This report describes successful treatment of myocardial infarction from coronary thrombosis in an infant with Kawasaki disease using intravenous tissue plasminogen activator and abciximab.

Reduced Proximal Aortic Compliance and Elevated Wall Shear Stress Following Early Repair of Tetralogy of Fallot

Objective: Patients with tetralogy of Fallot are at risk for late aortic complications due to progressive aortic root dilation and decreased aortic compliance. Early repair normalizes aortic dimensions by preadolescence. It is not known if early repair normalizes aortic wall histology and compliance or reduces late aortic complications. We used 4‐dimensional flow magnetic resonance imaging to determine if children with tetralogy of Fallot repaired in infancy had normal aortic dimensions and to characterize the aortic wall hemodynamic state and luminal flow parameters in these patients. Methods: Comprehensive aortic analysis with 4‐dimensional flow magnetic resonance imaging was performed in 18 patients with tetralogy of Fallot who were repaired in infancy and compared with 18 normal volunteers. Peak systolic and time‐averaged wall shear stress, relative area change, and distensibility were evaluated in standardized aortic planes. Qualitative grade scale flow analysis with interactive pathline visualization was used to detect pathologic flow patterns. Results: Thoracic aortic dimensions did not differ between groups, and all tetralogy of Fallot aortas were in normal range. In the tetralogy of Fallot group, ascending and descending aortic relative area change and distensibility were significantly reduced, and both peak systolic and time‐averaged wall shear stress were elevated throughout the aorta. Supra‐physiologic systolic helical formations occurred in the ascending aorta of 14 patients with tetralogy of Fallot (78%) versus 0 controls. Conclusions: Despite early repair and normal aortic dimensions, preadolescents and adolescents with tetralogy of Fallot had elevated wall shear stress, increased stiffness, and pathologic systolic flow formations in the proximal aorta. Although early repair normalizes aortic dimensions in childhood, our findings suggest that patients with tetralogy of Fallot remain at risk for late aortic complications.

Impact of Aortic Stiffness on Ventricular Function in Patients with Fontan Circulation

Objective Elastic properties of the thoracic aorta are responsible for buffering systemic afterload, and may be particularly important in patients with Fontan circulation, in whom heart failure is a major source of attrition. The purpose of this study was to characterize regional stiffness in the ascending and descending aorta in patients with hypoplastic left heart syndrome and single left ventricle morphology after Fontan operation by cardiac magnetic resonance imaging, and to assess whether changes in aortic stiffness are associated with the ventricular function. Methods Phase‐contrast‐derived pulse‐wave velocity (PWV) and relative‐area change (RAC) were measured in the ascending and descending aorta of patients with hypoplastic left heart syndrome (n = 9), patients with single left ventricle circulation (n = 18), and normal controls (n = 8) by magnetic resonance imaging. Stiffness metrics were then correlated with the ventricular volumetric and functional indices. Results Patients with hypoplastic left heart syndrome had elevated ascending aortic PWV along with reduced RAC when compared with controls (both P values < .001). Patients with a single left ventricle presented no change in PWV but had reduced RAC in comparison to controls (P < .01). There were no differences in PWV and RAC between all considered groups in the descending aorta. PWV and RAC measured in the ascending aorta correlated with end‐systolic and end‐diastolic volume indices, ventricular ejection fraction, and ventricular‐vascular coupling ratio. Conclusions Aortic stiffness is most elevated in patients with hypoplastic left heart syndrome, yet patients with single left ventricle morphology show signs of abnormal stiffness as well in the form of reduced aortic strain. Stiffness indices measured in the ascending aorta were associated with overall ventricular function and measures of aortoventricular coupling in both patient populations.

Children with kawasaki disease present elevated stiffness of great arteries: Phase-contrast MRI study: Elevated Stiffness of Great Arteries in KD

Patients with diagnosed Kawasaki disease (KD) are known to develop extracardiac vascular lesions and are prone to accelerated stiffening of medium‐size arteries.

Myocardial Perfusion Reserve Index in Children With Kawasaki Disease: Myocardial Perfusion in Kawasaki Disease

Coronary artery lesions in patients with Kawasaki disease (KD) can impair myocardial perfusion, yet evaluation of perfusion defects by cardiac magnetic resonance (MR) in children is often qualitative.

Impact of different coarctation therapies on aortic stiffness: phase-contrast MRI study

Coarctation of the aorta has been associated with increased thoracic aortic stiffness in adolescents and young adults. However, the effects of different therapeutic strategies on aortic stiffness in a young population is unknown. This study aimed to non-invasively assess aortic stiffness between different repair or intervention strategies in patients with coarctation of the aorta. Forty-nine coarctation patients who underwent either surgery (n = 26), balloon angioplasty (n = 14), or stent implantation (n = 12), and 26 age- and size-matched normotensive healthy controls underwent evaluation of thoracic aortic stiffness and flow hemodynamics via phase-contrast cardiac magnetic resonance. In children who had undergone surgical repair or balloon angioplasty, ascending aortic stiffness was increased when measured via pulse wave velocity (PWV) when compared to normal controls (all P < 0.05). Furthermore, ascending aortic distensibility and relative area change (RAC) was significantly lower in surgically and balloon treated groups (both P < 0.01). Stiffness (PWV), distensibility, and RAC in the ascending aorta were not statistically different between stented patients and controls. The ascending aorta of children following surgical repair or balloon angioplasty demonstrated signs of elevated stiffness, whereas those treated by stent implantation showed no difference in stiffness markers when compared to normal controls.

Proximal pulmonary vascular stiffness as a prognostic factor in children with pulmonary arterial hypertension

Aims Main pulmonary artery (MPA) stiffness and abnormal flow haemodynamics in pulmonary arterial hypertension (PAH) are strongly associated with elevated right ventricular (RV) afterload and associated with disease severity and poor clinical outcomes in adults with PAH. However, the long-term effects of MPA stiffness on RV function in children with PAH remain poorly understood. This study is the first comprehensive evaluation of MPA stiffness in children with PAH, delineating the mechanistic relationship between flow haemodynamics and MPA stiffness as well as the prognostic ability of these measures regarding clinical outcomes. Methods and results Fifty-six children diagnosed with PAH underwent baseline cardiac magnetic resonance (CMR) acquisition and were compared with 23 control subjects. MPA stiffness and wall shear stress (WSS) were evaluated using phase contrast CMR and were evaluated for prognostic potential along with standard RV volumetric and functional indices. Pulse wave velocity (PWV) was significantly increased (2.8 m/s vs. 1.4 m/s, P < 0.0001) and relative area change (RAC) was decreased (25% vs. 37%, P < 0.0001) in the PAH group, correlating with metrics of RV performance. Decreased WSS was associated with a decrease in RAC over time (r = 0.679, P < 0.001). For each unit increase in PWV, there was approximately a 3.2-fold increase in having a moderate clinical event. Conclusion MPA stiffness assessed by non-invasive CMR was increased in children with PAH and correlated with RV performance, suggesting that MPA stiffness is a major contribution to RV dysfunction. PWV is predictive of moderate clinical outcomes, and may be a useful prognostic marker of disease activity in children with PAH.

Aortic stiffness in adolescent Turner and Marfan syndrome patients

OBJECTIVES Turner syndrome (TS) and Marfan syndrome (MFS) are partially characterized by aortopathies with a risk of developing severe aortic dilation, stiffness and consequent dissection and aneurysm formation. The incidence of a bicuspid aortic valve (BAV) is also increased in TS. We investigated aortic stiffness in teenage TS and MFS patients and evaluated to what degree stiffness in TS patients is augmented by the presence of a BAV. METHODS Fifty-seven patients with TS (n = 37) and MFS (n = 20), as well as 22 controls with similar age and size distribution underwent evaluation of thoracic aortic stiffness using phase-contrast magnetic resonance imaging. Calculated stiffness indices including pulse wave velocity (PWV), distensibility and relative area change (RAC) were collected to characterize the ascending aorta and descending aorta. PWV was also determined to evaluate global aortic arch stiffness. RESULTS Patients with TS had reduced distensibility (0.43 vs 0.58%/mmHg, P < 0.05) and RAC (21 vs 29%, P < 0.01) in the ascending aorta when compared with normal controls. Similarly, patients with MFS had reduced ascending aortic distensibility (0.39 vs 0.58%/mmHg, P < 0.05) and RAC (22 vs 29%, P < 0.05). There were no differences in measured PWV in the ascending aorta. Patients with TS had significantly elevated PWV measured in the aortic arch when compared with controls (2.7 vs 1.9 m/s, P < 0.05). Patients with MFS had more prominent elevation in aortic arch PWV (4.2 vs 1.9 m/s, P < 0.01). The descending aortas had decreased distensibility (0.36 vs 0.55%/mmHg, P < 0.05) and RAC (18 vs 25%, P < 0.01) only in MFS patients. Additionally, 18 TS patients with a BAV were compared with 19 TS patients with a trileaflet aortic valve, without significant differences observed in any of the considered stiffness indices. CONCLUSIONS TS and MFS teenage patients display evidence of increased aortic stiffness. In TS patients, this is focused in the ascending aorta and is independent of the presence of a BAV. MFS patients display a generalized reduction in compliance of the entire aorta.